Multi-analytic approach to the understanding of the patho-physiology of retinitis pigmentosa and related diseases using genetic, immunologic and clinical imaging methods

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To gain insight into the detailed patho-physiology of retinitis pigmentosa (RP), retinal degenerative disease with rod photoreceptor loss, we studied 250 patients with typical RP using genetic, immunologic and clinical imaging analysis. First of all, we established the labor-and cost efficient genetic diagnostic system using WAVE d-HPLC system (Transgenomic co.). The system enabled us to screen for 29 reported causal genes of RP followed by direct sequencing to confirm the presence of specific gene mutation. Although we collected the patients regardless their familial background, among the 250 patients tested, we detected possible causal gene alteration in 30 patients. This frequency is as high as the frequency of known gene mutation among autosomal dominant RP patients alone which is considered to give the highest detection frequency. In our study, RHO, RDS, FSCN were the most frequent candidates as causal genes, which was compatible with previous reports in Japan, indicating the prac … More ticality of our gene diagnostic system. The relevance of novel gene alterations detected in our study and the disease should be further evaluated. We then tested the serum antibody titer against recoverin in RP patients to check the autoimmunity against self-retinal antigen using ELISA. In many RP patients, anti-recoverin antibody titer was increased compared to that in patients with age-related macular degeneration. Some of the patients with high antibody titer showed visual field loss unproportinal to the retinal atrophy area, and some of these patients had had a period of transient and rapid worsening of the disease in their disease history. These indicated a possible involvement of autoimmune reaction secondary to retinal degeneration in the course of RP progress. We also evaluated the photoreceptor status (i.e. loss of outer segment) in RP patients using optical coherent tomography (OCT) and retinal auto-fluorescence which is considered to indicate the well-functioning retinal pigment epithelial cells (RPEs). The area of functional photoreceptors and that of functional RPEs did not correspond in some patients, indicating that in some patients, there is a discrepancy between the time of photoreceptor degeneration and that of RPE deterioration, although they make a concomitant complex. Less